Team:CPU CHINA/Safety
Safety
Safe Project Design
The original idea of our program came from a public health emergency—tuberculosis-- happened on a school campus. The tuberculosis is a widespread infectious disease, whose outbreak tightly relates to the safety of every citizen within certain area. The aim for further controlling the contamination of M. tuberculosis results in our I-like system targeting on a life-threatening issue.
Though tuberculosis has already became a vague concept for many people, since it has been steadily controlled in well-urbanized societies, which all contributes to the strict regulation of official public health departments as well as the discovery of drugs, however, with the evolution of pathogenic bacteria, the outbreak might still return. Therefore, we combine a cell therapy with the treatment for this disease.
General Safety in Laboratory
Before entering the lab, we need to have overall safety knowledge on how to use and maintain the devices correctly. Since our project requires intensive cell experiments, we need to carefully learn about the guidance on cell operation.
The first is to form a “concept of sterile”, make sure every action within the cell operation room minimize the possibility of introducing unwanted pollutions. Biological safety cabinet is the central place for conducting experiments. All consumable items must undergo corresponding sterile procedure before put into the biological safety cabinet. Cells must be kept in incubators unless during experiments or routine maintenance. The conditions of incubation must be stable and comply with the requirement of certain cell line. Turn on the ultraviolet light before experiment and after daily use. All these standard operating procedures can keep the cells sterile and avoid cross infection between experiment groups.
To better conduct experiments, a correct operating platform is vital as well. Our project includes usage of bacteria and non-primary cell lines, thus a biological safety cabinet should be equipped for sterile operating circumstances and the safety of lab members. Meanwhile gloves and uniforms can provide protection for operators as well as precious cells.
Other safety issues generally include the electricity, reagents and complicated devices. Read the manual carefully before everything starts can avoid many accidents, as well as elongate the expectations of devices.
Experiment Design
As is widely known, M. tuberculosis is a strong infectious pathogen that may threaten the safety of operators, also the safety policy has denied the possibility of using it, therefore we choose a substitution—M. smegmatis, which has similar pathogenic compounds but safe to operators—for any occasion that needs M. tuberculosis originally. Bacteria incubation usually involves enormous quantity far more than that under natural circumstance, any improper disposition will be a potent risk for environmental pollution. After experiments, the excess biofluid must be boiled for a certain time to minimize the transmission of bacteria outdoors, and all biosamples must be collected in an appointed container.
We use two kinds of cell lines in our experiments: HEK293T cell and Raw 264.7 cell line. Both cell lines are commonly used in many laboratories, and are of low risk, the main safety issue is to prevent cell pollution during the incubation period, considering that cross infection can bring about widespread negative effects on other users who share one cell operation room.
Safe Application
All things are considered with safety. If our project turns into practice, there will be an extra choice for treatment of tuberculosis, with a new application vehicle: modified cells. Suppressing the incidence of tuberculosis does help to keep the emergence of public health issue at a minimal rate, as tuberculosis is a severe infectious diseases, this is a vital contribution to the society. Also, the cells can be naturally eliminated with the time goes by, the effect of modulated cells wouldn’t exist permanently. After the proof of action of the whole system, we will consider adding a suicide parts to stall the expression of those cells at a specific time, in case of any required situations. In addition, there is also a vital part: the immunogenicity brought by modified cells remains to be considered. Stem cells have been widely applied into a series of cell therapies, due to their good compatibility with the immune system of the hosts [1]. Therefore, we might consider building up our I-like system based on a proper type of stem cell for application to patients.
With the development of cell therapy in clinical use, there are blooming amount of regulations and acts to supervise the standard application of this special therapy. As many types of potent cells are originated from body and requires human donors, a series of regulations are needed [2]. The cells extracted from bone marrow, peripheral blood and cord blood should follow the international standards established by the Foundation of Applied Cell Therapy (FACT), American Association of Blood Bank (AABB), College of American Pathologists (CAP) and so on [3]. For example, we will directly aim at the standards of FACT-JACIE (Joint Accreditation Committee) International Standards for Hematopoietic Cellular Therapy Product Collection, Processing, and Administration, which covers the extraction, proceeding, storage and application of blood products from cord or peripheral blood. Current Good Organized Practice (cGTP) also stipulated production requirements including facilities, environments, reagents and processing etc. [4]. Under the regulation of these guidance, the safety of our product can be firmly guaranteed along with the promise of efficacy of treatment.
Above all, this cell therapy is prone to be a next-generation measure for treatment of tuberculosis.
References
[1] Buzhor E, Leshansky L, Blumenthal J, et al. Cell-based therapy approaches: the hope for incurable diseases[J]. Regenerative Medicine, 2014, 9(5): 649-672.
[2] Eva D. Q. Transfusion Medicine and Hemostasis (Second Edition)(2013),(577-584).
[3] AABB (2009). AABB Standard for Cellular Therapy Products, 4th edition, AABB, Bethesda, MD, USA.
[4] Foundation for the Accreditation of Cellular Therapy (FACT) (2012). FACT-JACIE International Standards for Cellular Therapy Product Collection, Processing, and Administration, 5th edition, FACT, Nebraska, USA.